The invention pertains to the field of obtaining and isolating physiologically active chemical compounds from natural sources. Specifically, the invention pertains to the field of obtaining and isolating taxanes, including paclitaxel.
Paclitaxel is the active ingredient in the anticancer drug TAXOL® (“taxol”) marketed by Bristol-Myers Squibb Company (New York, N.Y.). Taxol has been approved for treatment of ovarian and breast cancers, Kaposi's sarcoma, and non-small-cell lung cancer. It is also in clinical trial for treatment of several other cancers in combination with other chemotherapeutic agents. Several other uses for paclitaxel have been identified, including possible treatments for psoriasis, polycystic kidney disease, multiple sclerosis, and Alzheimer's disease, and for coating stents inserted into blood vessels following angioplasty.
Paclitaxel is a complex diterpenoid compound originally extracted from the bark of the Pacific yew tree, Taxus brevifolia. A number of related compounds, collectively known as “taxanes,” are also found in the yew extract. Paclitaxel is currently obtained from various species of yew or is made by partial synthesis from other taxanes also obtained from yew. Durzan, U.S. Pat. No. 5,670,663 discloses that taxanes are produced in conifers other than yew, including Araucaria excelsa, Araucaria angustifolia, Fitzroya cupressoides, Picea abies, and Cupressus sempervirens. In addition to conifers, sources of taxanes have been identified in ginkgo (Ginkgo biloba) and hazelnut (Corylus spp.) trees.
Strobel, U.S. Pat. No. 6,329,193, incorporated herein by reference, discloses the production of taxanes from fungi and methods of obtaining such fungal-produced taxanes. Several U.S. patents including Foo, U.S. Pat. No. 6,136,989, incorporated herein by reference, disclose methods for extraction of paclitaxel from paclitaxel-containing materials, including from plant tissue and from microorganisms.
Yields of taxanes from these sources are very low, necessitating the continuing search for additional sources of taxanes, especially of taxol.